Med chem
ANTI-ARRHYTHMIC DRUGS It is the improper beating of the heart, whether irregular, too fast, or too slow.
Normal range of heart beat: 60–100 bpm (normally about 72 bpm).
It occurs when electric impulses in the heart do not work properly.
Also occurs due to other heart diseases such as myocardial ischemic disease, etc.
Causes of Arrhythmia
Bradycardia (Reduced Automaticity)
↑ Parasympathetic system Sleeping Disease (Heart disease) Other drugs such as Beta blockers, antiarrhythmic drugs, etc. Conduction Block
• ↑ Refractory period
Types of arrhythmia
1 Atrial flutter (AFl): A condition in which our heart’s upper chamber (atria) beats too quickly (about 200–350 bpm).
2 Atrial fibrillation (AF): An irregular, mostly rapid heart beat (about 350–550 bpm). It is due to abnormal twitching of heart muscles.
Classification of anti arrhythmic drugs
Class-l: Membrane stabilizing agents /
Na+ channel blockers
Mechanism of Action (MOA): Inhibit the influx of Nat, which is responsible for depolarization. Due to inhibition, the concentration of Na+ inside the cell decreases, causing a decrease in depolarization (Phase 0), giving time for our heart to relax or normalize.
Class-II: Beta blockers Drugs: Propranolol, Esmolol, Atenolol, etc.
Class-III: Potassium Channel Blockers
MOA: These drugs block the Potassium (K+) channel, which inhibits the outflow of IK, ion. Due to this,
phase 3 (repolarization) is prolonged, the duration of the Action Potential is prolonged, and the effective refractory period is prolonged. Also prolongs the QT interval.
Drugs: Amiodarone, Sotalol, etc
Class-IV: Calcium channel blockers (Non-DHPs)
Drugs: Verapamil, Diltiazem, etc.
●●●ANTI-HYPERLIPIDEMIC AGENTS
These are those drugs which are used in the treatment of hyperlipidemia. Also known as lipid-lowering agents or hypolipidaemic drugs.
Hyperlipidemia is a condition in which the plasma level of lipid is elevated (increases) in the form of Lipoproteins. This hyperlipidemia causes atherosclerotic plaque (atheroma), which further causes heart attacks, strokes, and many other heart diseases.
Causes: Being overweight (obesity), smoking & stress, diet, being stressed.
Lipids: Important for our body; present in three forms:
●●●Classification of hyperlipidmic agents 1. Fibrates
• Clofibrate: Belongs to the class of fibrates (derivatives of fibric acid). It decreases triglyceride levels and increases HDL levels.
MOA: Clofibrate binds and activates Peroxisome Proliferator-Activated Receptor alpha (PPARæ), a nuclear receptor family regulating lipid metabolism. This increases lipoprotein lipase enzymes, which degrade triglycerides, decreasing hepatic VLDL and LDL production and increasing HDL.
Uses: Treatment of hypertriglyceridemia and controlling cholesterol/lip in levels.
HMG Co-A Reductase Inhibitors (Statins)
• Lovastatin: Belongs to the class of statins.
MOA: Lovastatin inhibits the enzyme HMG-CoA reductase, which is the rate-limiting step (slowest step) of cholesterol synthesis, reducing cholesterol production.
When the liver senses decreased cholesterol, it activates/increases LDLR, binding more circulating LDL, reducing its level in blood circulation and clearing atheromas.
Uses: Controls high plasma levels of cholesterol & lipids, prevents coronary artery disease and cardiovascular diseases.
3 Bile Acid Sequestrants (Resins)
• Cholestyramine: Belongs to the class of bile acid sequestrants.
●●●COAGULANTS AND ANTI-COAGULANTS
●●●Coagulants: Substances or drugs which promote blood clotting.
Anti-coagulants: Substances which prevent blood clotting.
Haemostasis:
Haemo (connected to blood) + stasis (stable Sequences of responses that stop bleeding when blood vessels are damaged or ruptured.
Drugs 1. Coagulants
• Menadione (Vitamin K3 – Synthetic):
MOA: Vitamin K is required for the synthesis of clotting factors II, VII, IX, and X (y-glutamyl carboxylase pathway). Menadione promotes coagulation.
• Uses: Treatment of bleeding, increasing coagulation, and vitamin K deficiency.
Acetomenadione: Synthetic analogue of Vitamin K、. MOA and uses are same as Menadione.
Anticoagulants
Warfarin (Oral Anticoagulant):
MOA: Interferes with Vitamin K-dependent synthesis of clotting factors (II, VII, IX, X) in the liver by blocking Vitamin K Reductase, preventing the recycling of Vitamin K epoxide back to its active hydroquinone form.
SAR: 1. OH group at position 4 is essential. An SH group can be attached but reduces activity.
2Coumarin ring is essential. Positions 3 and 4 are responsible for active derivatives.
3Ketone chain of 3 carbons produces potent compounds. Replacing it with an alkyl group produces less potent compounds.
4Phenyl ring is essential. Replacement with a long alkyl group increases activity.
Antiplatelet Drugs (Blood Thinners) • Clopidogrel:
MOA: Inhibits the binding of ADP to its P2Y12 receptor on platelets, preventing ADP-mediated activation of the GPIIb/Illa complex, thereby inhibiting platelet activation and aggregation.
Uses: Antiplatelet medicine to prevent blood clots, heart attacks, and strokes.
Moa of warfarin It interfare with vit .K dependent Synthesises of clotting factor (II, I, IS, 3 in liver by blocking the vit.K reductase Which further inhibit the blood coagutation
●●●Congestive Heart Failure (CHF)
A progressive condition in which the heart doesn’t pump blood in a sufficient amount (↓ Cardiac Output)
Symptoms: Shortness of breath, fatigue, swollen legs, rapid heartbeat, chest pain, dizziness, etc.
Causes/Risk Factors: Coronary Artery Disease, Hypertension, alcohol abuse, viral infections, thyroid disorders, diabetes, smoking, family history, heart valve disease.
Types of CHF
Left-sided CHF (Most Common): Left ventricle does not pump blood properly, causing fluid backup in the lungs (breathing difficulty).
Systolic HF: Left ventricle fails to contract (↓ force of contraction).
Diastolic HF: Left ventricle fails to relax due to muscle stiffness (No relaxation = no filling).
Right-sided CHF: Right ventricle does not pump blood properly into the lungs. Causes fluid retention in lower extremities, abdomen, and other vital organs. Often develops as a result of left-sided CHF.
Drugs
Cardiac Glycosides (Digitalis)
Digoxin / Digitoxin (+ Inotropic):
MOA: Inhibits the Na+/K+ ATPase enzyme on myocardial cells. This stops Nat outflux, causing Nat to accumulate inside the cell. The Na+/Ca2+ exchanger reverses its direction to pump Nat out and influx Ca2+ in. The accumulated intracellular Ca2+ triggers a larger release of calcium from the Sarcoplasmic Reticulum (SR), increasing calcium concentration which enhances the force of contraction (positive inotropic effect).
●●●DIABETES MELLITUS
Diabetes Mellitus is a chronic metabolic disorder characterized by high levels of Glucose in Blood.
It occurs either due to inadequate production of Insulin by Pancreas or body’s inability to effectively use Insulin.
Insulin is a Hormone produced by Pancreas that helps to regulate Blood Sugar Level by facilitating absorption of Glucose into cells to be used for Energy.
Causes 1. Genetic Mutations 2. Viral Infections
Early Childhood Exposures 4. Geographical & Seasonal Patterns
SYMPTOMS Increased Thirst Frequent Urination Extreme Hunger Weight Loss Fatigue Weakness
●●●ANTIDIABETIC AGENTS
Antidiabetic Agents are used for treating Diabetes Mellitus by decreasing blood glucose levels.
Some of these drugs are administered orally and termed Oral Hypoglycaemic or Oral Antihyperglycaemic Agents.
Different classes of anti-diabetic drugs exist and they are selected based on nature of diabetes, individual’s age, situation and other factors.
INSULIN
Insulin is a peptide hormone that plays a central role in regulating various metabolic processes, particularly the regulation of blood glucose levels.
It is produced & secreted by beta cells of islets of Langerhans in pancreas.
Insulin is essential for proper utilization, storage and regulation of glucose and other nutrients in the body.
CLASSIFICATION OF ORAL HYPOGLYCAEMIC AGENTS
1Sulfonyl Ureas Tolbutamide * Chlorpropamide Glipizide Glimepiride 2 Biguanides Metformin3Thiazolidinediones
Pioglitazone Rosiglitazone 4 MeglitinidesRepaglinide
Nateglinide
A-Glucosidase Inhibitors Acarbose Voglibose
●MOA Sulfonylureas bind to and inhibit the ATP-sensitive potassium channels (KATp) on cell membrane of pancreas.
This inhibition causes membrane depolarization, leading to opening of voltage-gated calcium channels.
The resulting influx of calcium triggers the exocytosis of insulin granules, increasing insulin secretion.
●●●LOCAL ANAESTHETICS
A Local Anaesthetic is a medication used to temporarily numb a specific area of the body, preventing pain sensation without affecting consciousness.
It works by blocking nerve signals in the area where it is applied or injected
CLASSIFICATION OF LOCAL ANAESTHETICS
Benzoic Acid Derivatives
Cocaine, Hexylcaine, Meprylcaine, Cyclomethycaine, Piperocaine 2. Amino Benzoic Acid Derivatives
Benzocaine *, Butamben, Procaine Butacaine, Propoxycaine, Tetracaine, Benoxinate 3. Lidocaine / Anilide Derivatives Lignocaine (Lidocaine), Mepivacaine, Prilocaine, Etidocaine 4. Miscellaneous • Phenacaine, Diperodon, Dibucaine *
SAR OF BENZOIC ACID DERIVATIVES
General Structure:
Aromatic Ring (Lipophilic) – Intermediate
Aromatic Ring: Provides lipophilicity. Electron Donating Groups enhance activity, while Electron Withdrawing Groups reduce it.
Intermediate Chain: Increasing chain length enhances lipid solubility and nerve penetration.
3. Amino Group: Tertiary amines are the most useful. Secondary amines have a longer duration but are irritating; primary amines are not active
●●●Stereochemistry & Metabolism
STEREOCHEMISTRY OF STEROIDS
There are 6 asymmetric carbon atoms (5, 8, 9, 10, 13, 14) in the steroid nucleus, therefore 64 optically active forms are possible. Cholestane, androstane & pregnane exist in two conformations:
Chair form is more stable than boat form due to less angle strain, therefore all cyclohexane rings in the steroid nucleus exist in chair form
Cis & Trans Form
Cis form indicates substituents on the same side of the ring while trans form has substituents on the opposite
Cis Form (Substituents on the same side)
Trans Form (Substituents on opposite sides)
STEROID METABOLISM
Steroid Metabolism refers to the breakdown and transformation of steroids in the body
All the steroids in the human body are synthesized from cholesterol. Steroid metabolism occurs in various tissues including liver, kidneys, and adrenal gland, catalyzed by enzymes such as Cytochrome P450, hydroxysteroid dehydrogenases & sulfotransferases.
●Hydroxylation Reduction Oxidation Methylation
Sulfation Glucuronidation
Sex hormones
Testosterone
Testosterone is a steroid hormone classified as Androgen, primarily produced in testes in males and in smaller amounts by the ovaries in females and the adrenal gland in both SexeS.
It is the primary male sex hormone, playing a crucial role in various body functions, including development of male reproductive tissues, maintenance of secondary sexual characteristics (like facial hair, deeper voice, muscle mass) & regulation of libido, bone density & red blood cell production.
MOA (Mechanism of Action)
Testosterone binds to specific androgen receptors in target cells, forming a testosterone-receptor complex that regulates gene expression, leading to changes & promotion of protein synthesis that causes growth & development of masculine sex organs & secondary sexual characteristics.
Nandrolone 3 Progesterones 4Oestriol 5 Oestradiol
●●●ERECTILE DYSFUNCTION
Erectile Dysfunction, also termed as Impotence, is defined as failure to achieve or maintain a rigid penile erection suitable for satisfactory sexual
intercourse. It is a common condition in men aged over 40 years, but it can affect men of all ages.
●CAUSES stress anxiety depression relationship problems self esteem unhealthy lifestyle performance anxiety
Drug ●● Sildenafil
Sildenafil is sold under the brand name Viagra with vasodilating & anti-inflammatory properties.
MOA
Sildenafil acts by blocking phosphodiesterase-5 (PDE-5) enzyme that promotes breakdown of cyclic guanosine monophosphate (cGMP) which regulates blood flow in the penis..
●●●An Oral Contraceptive, often referred to as “the pill”, is a medication taken by mouth to prevent pregnancy.
They prevent pregnancy by inhibiting ovulation and also by preventing sperm from penetrating through the cervix. Types1 Combined Oral Contraceptive 2.Progestin-Only Pills
COMBINED ORAL CONTRACEPTIVE
• It consists of a combination of Estrogen & Progestin.
They work by:
Preventing Ovulation
Thickening cervical mucus to block sperm from reaching the egg. Thinning the uterine lining to reduce the likelihood of implantation
PROGESTIN ONLY PILLS (MINI PILLS)
They are often used by individuals who cannot take estrogen.●They primarily work by thickening cervical mucus & sometimes inhibit Ovulation
●●●Thyroid hormones are essential chemical messengers produced by the thyroid gland, a small butterfly-shaped gland located in front of the neck.
The Thyroid Gland is the source of two fundamentally different types of hormones.1Thyroxine 2 Triiodothyronine
Both hormones are vital for normal growth & development and control essential functions, such as energy metabolism and protein synthesis.
The Thyroid Gland is divided into lobules which consist of mainly two types of cells:
1 Follicular Cells 2 Parafollicular Cells
THYROID DRUGS L-Thyroxine L-Thyronine
ANTITHYROID DRUGS
Propylthiouracil Methimazole
L-THYROXINE
L-Thyroxine (also known as Levothyroxine) is a synthetic form of the thyroid hormone Thyroxine (T4), which is normally produced by theThyroid Gland.
It is the treatment of choice for hypothyroidism.
MOA
L-Thyroxine is a synthetic T4. First, it is
converted to its active form Triiodothyronine (T3) in peripheral tissues, then it binds to nuclear thyroid receptors, where it regulates gene expressions to perform various physiological functions.
L-THYRONINE
L-Thyronine is a synthetic Triiodothyronine (73) that plays a crucial role in various physiological processes
MOA
L-Thyronine is a synthetic T3 that binds to thyroid hormone receptors in the nucleus of cells & regulates various physiological processes.
Uses
• Severe Hypothyroidism
Propylthiouracil
PROPYLTHIOURACIL
Propylthiouracil is an antithyroid drug primarily used in the treatment of hyperthyroidism, including conditions like Graves’ Disease
MOA
It inhibits the Thyroid Peroxidase enzyme, preventing iodination of tyrosine residues, synthesis of thyroid hormones, and also inhibits T4 to T3 peripheral conversion.